V 


PREPARATION  OF  CERTAIN  DERIVATIVES  OF  PHENYL 
ARSINE,  AND  THEIR  REACTION  WITH  ALDEHYDES 

BY 

SAMUEL  MARION  McELVAIN 
B.  S.,  Washington  University, 

1920 


THESIS 


Submitted  in  Partial  Fulfillment  of  the  Requirements  for  the 


Degree  of 

MASTER  OF  SCIENCE 
IN  CHEMISTRY 


IN 


THE  GRADUATE  SCHOOL 

OF  THE 

UNIVERSITY  OF  ILLINOIS 


1921 


N\\-^ 

UNIVERSITY  OF  ILLINOIS 


THE  GRADUATE  SCHOOL 


May  27  J 


I HEREBY  RECOMMEND  THAT  THE  THESIS  PREPARED  UNDER  MY 


BE  ACCEPTED  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR 
THE  DEGREE  OF ^>iiAtLCEH-CLb’  BCIMHCS 


Recommendation  concurred  in* 

Committee 

on 

Final  Examination* 


*Required  for  doctor’s  degree  but  not  for  master’s 


Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/preparationofcerOOmcel 


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- 1 - 

It  has  heen  recently  found  that  phenyl  arsine  can  he  con- 
densed with  aldehydes  in  the  presence  of  a small  amount  of  hydro- 
chloric acid  to  give  definite  and  relatively  stable  addition 
products.  The  reaction  is  between  one  mol  of  the  arsine  and  two 
mols  of  the  aldehyde  and  goes  probably  according  to  the  follow- 
ing equation: 

CsHsAsHg  2RCH0  > GeHsAsCCHOHR)  ^ 

By  this  reaction  condensation  products  between  phenyl  arsine 

(1) 

and  butyraldehyde  and  benzaldehyde  have  been  prepared. 

The  discovery  of  this  new  series  of  organic  arsenic  com- 
pounds immediately  suggested  the  possible  therapeutic  value  of 
some  of  them.  Consequently  it  was  the  purpose  of  the  work  with 
which  this  paper  deals  to  prepare  an  alkali  soluble  arsine  and 
to  attempt  condensations  of  it  with  various  aldehydes.  Such 
condensat  ion  ..products  would  have  water  soluble  salts  and  there- 
fore be  capable  of  therapeutic  testing. 

p-Carboxyphenyl  arsine  was  chosen  as  the  arsine  to  be 
employed.  This  arsine  should  give  a series  of  alkali  soluble 
addition  products  of  the  general  f ormula  p-H00CC6H4As(CH0HR) 2 . 

It  was  found,  however,  that  condensations  could  not  be  brought 
about  to  any  appreciable  extent  between  this  arsine  and  acet- 
aldehyde or  benzaldehyde,  when  the  same  conditions  under  which 
phenyl  arsine  condenses  were  enployed.  In  the  case  of  benzalde- 
hyde a small  amount  of  what  appeared  to  be  an  addition  product 
(1^  Adams"  and  Palmer,’  J . ■Ame'r.  Chem,  Soc.,  42,  2375  (1920)' 


was  isolated,  but'  it  differed  from  the  compound  expected  in  that 
there  was  no  free  carboxyl  group  present.  The  compound  also 
appeared  to  be  unstable,  for  its  arsenic  content  consistently 
decreased  after  each  crystallization  from  hot  acetone. 

EXT^ERTMENTAL . 

Preparation  of  n-Benzarsonic  Acid.  HOOC-CfiHAAsOr>Hr>{'D)  . 

This  acid  was  prepared  by  two  different  methods,  (a)  the  oxida- 
tion of  p-tolylarsonic  acid  and  (b)  from  p-amino  benzoic  acid 
by  diazo  reaction. 

Sieburg^lias  reported  quantitative  yields  of  p -benzarsonic 
acid  from  the  oxidation  of  p-tolylaraonic  acid,  with  nitric  acid 
(d*1.3)  in  a sealed  tube  at  170® C.  Such  a method  would  not, 
however,  be  very  practical  for  the  preparation  of  fairly  large 
quantities  of  the  acid.  Instead  of  nitrio  acid  alkaline  perman- 
ganate was  substituted  as  an  oxidizing  agent.  PotassiuM' perman- 
ganate (28g.),  p-tolylarsonic  acid  (20g.)  and  sodium  hydroxide 
(I2g.)  were  dissolved  in  about  1500  cc.  of  water  and  the  oxi- 
dation allowed  to  proceed  at  room  temperature.  After  about  two 
weeks  the  colorless  solution  was  filtered.  The  filtrate  was 
acidified  (to  Congo  red)  with  hydrochloric  acid  and  evaporated 
to  about  100  cc.  iihen,  upon  cooling  to  5®C.,  crystals  of  p-benz- 
arsonic  acid  separated  out.  This  acid  is  readily  separated  from 
any  p-tolylarsonic  acid  by  the  fact  that  the  sodium  salt  of  the 

'latter  is  soluble  in  alcohol  while  the  corresponding  salt  of  the 
(l)  Sieburg,  Arch.  Pharm.,  254,  224  (1916). 


- 3 - 

benzarsonic  acid  is  insoluble.  The  yield  by  this  procedure  is 
about  18  g.  (60^  of  theory) . 

For  the  preparation  of  p-benzar sonic  acid  from  p -amino  benzoic 

(1)  (2i 

acid  a modification  of  Barts  reaction  was  employed.  One  mol 
of  p-amino  benzoic  acid  was  dissolved  in  a liter  of  water  con- 
taining l.S  mol 3 of  hydrochloric  acid.  This  solution  was  cooled 
to  about  0°C.  and  a saturated  solution  of  one  mol  of  sodium 
nitrite  was  slowly  run  in  from  a funnel.  The  solution  was 
stirred  vigorously  by  a motor  during  diazot ization.  The  diazo 
solution  thus  prepared  was  then  slowly  siphoned  into  an  arsenite 
solution,  made  by  dissolving  one  mol  of  arsenic  trioxide  and  one 
mol  of  sodium  carbonate  in  about  800  cc.  of  hot  water  to  which 
10  g.  of  CUS04.5H20  was  added  as  a catalyst.  During  this  reaction 
the  solution  was  stirred  vigorously  and  the  temperature  kept  be- 
tween 12o-15©C.  with  cracked  ice.  After  all  the  diazo  solution 
had  bean  added  the  reaction  mixture  was  placed  on  a steam  cone 
and,  with  continued  stirring,  heated  at  a temperature  bf  60® C. 
for  one  hour.  UlThile  still  hot  the  reacEtion  mixture  was  acidified 
to  Congo  red  with  hydrochloric  acid  and  filtered.  A dark  red  by 
product  is  removed  by  this  filtration  leaving  a clear  straw 
colored  filtrate.  It  is  important  that  the  reaction  mixture 
be  acidified  at  least  to  congo  red,  otherwise  the  filtrate  will 
contain  some  of  the  red  by  product  which  is  very  hard  to  separate 

from  the  benzarsonic  acid. 

(ll  Ind.  Eng.  Chem.  11,  824  (1919) 

(2)  D.  R.  P.  250624. 


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The  filtrate  was  then  concentrated  to  about  50Ooc.  and 
cooled.  The  benzarsonic  acid  separated  out  in  yellow  colored 
scales  which  were  decolorized  by  boiling  their  alkaline  solution 
with  bone  black.  The  yields  by  this  method  were  between  55-60^ 
oi  theory. 


Schmidt  has  reported  good  yields,  of  the  various  arsonic 
acids  using  sodium  hydroxide  instead  of  sodium  carbonate  in  the 
arsenite  solution.  Several  rans  were  made  using  sodium  hydrox- 
ide in  order  to  compare  the  relative  merits  of  the  two  alkalies. 
The  yields  obtained  were  much  poorer  than  those  given  by  sodium 
carbonate.  They  varied  from  10'^  to  35*^  of  theory,  and,  due  to 
the  increased  formation  of  the  red  by  product,  the  benzarsonic 
acid  was  much  harder  to  purify. 


This  arsine  has  been  prepared  by  Sieburg  by  the  active  reduction 
of  the  corresponding  arsonic  acid  in  methyl  alochcl  with  zinc 
and  hydrochloric  acid.  Both  ether  and  methyl  alcohol  ?;ere 
tried  in  this  work  as  solvents  for  the  acid  with  the  result  that 

methyl  alochol  was  found  to  be  much  the  better.  The  main  diffi- 
culties with  the  ether  appeared  to  be  its  volatility  at  the 
temperature  of  the  reaction  and  the  fact  that  it  was  not  a very 
good  solvent  for  the  arsonic  acid. 


(1) 


Preparation  of  r-Carboxvphenvl 


(1)  Schmidt,  A.,  421,  159(1920) 

(2)  Sieburg,  Arch.  Pharm.  254,224  (1916) 


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p-Benzareonic  acid  (50g.)  and  zinc  dust,  smalgamatad  with 
3 g.  of  mercuric  chloride  (400g.)  were  placed  in  a 3 liter  round 
bottom  flask  fitted  with  a stopper  carrying  a dropping  funnel 
and  a reflux  condenser.  The  upper  outlet  of  the  reflux  conden- 
ser carried  a mercury  trap.  Methyl  alcohol  (300  cc.)  was  run 
into  the  flask  thru  the  funnel  and  the  contents  of  the  flask  were 
warmed  until  the  arsonic  acid  went  into  solution.  Concentrated 
hydrochloric  acid  (l  1.)  was  then  slowly  dropped  into  the  flask 
at  a sufficient  rate  to  keep  “up  a fairly  vigorous  evolution 
of  the  gas.  The  time  required  for  the  addition  of  the  acid  was 
usually  about  8 hours.  After  the  acid  had  been  added,  the 
contents  of  the  flask  were  diluted  with  an  equal  volujne  of  water 
and  the  arsine  removed. 

Two  procedures  were  available  for  the  extraction  of  the 

arsine,  viz,  (a)  steam  distillation  and  (b)  extraction  from  the 

reaction  mixture  with  ether.  Owing  to  the  extreme  sensitivity, 

of  these  arsines  to  oxygen,  these  procedures  must  be  carried 

out  in  an  atmosphere  of  carbon  dioxide.  Steam  distillation  was 

found  to  have  a distinct  s^dvantage  over  ether  extraction  of  the 

reaction  mixture  because  the  ether  dissolved  substances 
the 

other.,  than /arsine  . These  substances  were  probably  other  re- 
duction products  of  the  arsonic  acid. 

^hen  the  reduction  mixture  was  subjected  to  steam  distilla- 
tion, a white  crystalline  condensate  separated  out  in  the  con- 
denser tube.  This  condensate  together  with  the  aqueous 


9 fX 


distillate  was  received  in  a 3 1 , filter  flask  containing 
300  cc.  of  ether.  The  distillation  was  kept  Tsp  with  carbon 

dioxide  passing  thru  the  system  until  no  more  of  the  arsine 
appeared  in  the  condensing  tube.  Fnen  this  stage  was  reached 
the  distillate  usually  amounted  to  about  one  liter.  The  ether 
layer  containing  the  arsine  was  separated  from  the  aqeueous 
portion  and  the  ether,  after  drying  over  anhydrous  sodium 
sulfate,  removed  in  a vacuum  desiccator.  Yield  10-15g.  (35-37'^ 
of  theory) . 

p -Garbo xyphenyl  arsine  crystallizes  from  ether  in  short 
white  prisms,  which  melt  at  79-80<>C.  in  an  atmosphere  of 
carbon  dioxide.  It  cannot  be  distilled  under  10  mm.  pressure 
without  decomposition  into  metallic  arsenic.  This  arsine 
behaves  quite  different  on  exposure  to  air  than  phenyl  arsine. 
The  latter  compound  is  oxidized  in  the  air  to  a mixture  of 
arseno  benzene  and  phenyl  arsinic  acid.  If  this  kind  of  change 
were  to  take  place  with  p-carbox^qjhenyl  arsine  an  alkali  sol- 
uble product  should  result.  Such  is  not  the  case,  however,  for 
on  exposure  to  air  p-carboxyl  phenyl  arsine  quickly  changes 
to  an  amorphous  yellow  compound  which  does  not  melt  under  300® 
and  which  is  insoluble  even  in  boiling  sodium  hydroxide. 

The  oxidation  is  evidently  accompanied  by  some  sort  of  conden- 
sation by  which  the  identity  of  the  carboxyl  group  is  destroyed. 


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7 


CONDE^JSATION  OF  p-CARBOrYPHENYL  ARSINE 
WITH  ALDEHYDES. 

Acetal dehvde'j  p -Garbo xyp he nyl  arsine  (15g.)  was  dis- 
solved in  100  cc.  of  ether  and  this  solution  transferred  to  a 
200  cc . Erlenmeyer  flask.  This  flask  was  fitted  with  a stopper 
carrying  an  inlet  and  outlet  tube  for  carbon  dioxide  together 
with  a small  dropping  funnel.  A few  drops  of  concentrated 
hydrochlcr icracid  were  added  as  a catalyst  to  the  ether  solu- 
tion and  then  paraldehyde  (7g.)  was  rum  in  from  the  funnel. 
During  this  pmcedure  a continuous  stream  of  carbon  dioxide 
was  kept  passing  thru  the  flask.  Almost  immediately  after  the 
addition  of  the  paraldehyde  to  the  arsine  solution  a yellow 
compact  precipitate  appeared.  This  precipitate  had  the  appear- 
ance of  the  compound  resulting  from  the  oxidation  of  the  arsine 
in  air,  in  that  it  was  insoluble  in  alkali  and  did  not  melt 
under  300<>C.  Similar  results  to  these  were  obtained  on  each 
attempt  to  condense  the  arsine  with  paraldehyde.  From  these 
facts  it  appears  that  acetaldehyde  instead  of  condensing, 
exerts  an  oxidizing  effect  rpon  the  arsine. 

Benzaldehyde . With  this  aldehyde  the  same  procedure  was 
followed  as  in  the  previous  case,  except  that  benzaldehyde 
(l5g.)  was  subsitututed  for  the  paraldehyde.  There  was  no 
immediate  precipitate,  but  on  standing  over  night  a white 
voluminous  precipitate  settled  out.  An  excess  of  benzaldehyde 


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ever  the  theoretical  amount  should  be  avoided,  for  it  was  found 
that  the  precipitate  was  quite  soluble  in  benzaldehyde-ether 
mixtures.  The  largest  yield  of  this  compound  obtained  was 
about  3 g.  from  runs  in  which  15  g.  of  the  arsine  was  used. 

This  condensation  product  was  very  bulky  and  crystallized 
from  hot  acetone  in  large  cotton-like  masses.  It  began  to 
shrivel  and  darken  at  234oC.  and  melted  with  the  evolution  of 
a gas  at  236-239oC.  Its  weight  was  unchanged  after  drying  at 
110®Q«for  two  hours.  It  was  insoluble  even  in  boiling  5'^  sod- 
ium hydroxide.  A most  peciiliar  property  of  the  substance,  in 
contrast  to  its  apparent  stability  when  heated  to  110© C.,  was 
its  consistent  loss  of  arsenic  upon  repeated  crystallizations 
from  hot  acetone.  The  arsenic  content  was  determined  by  the 


the  arsenic  content  was  14.4^  (theoretical  value  for 
HOOCCgHsAs (CHOHCsHg)  3 - 18. After  each  of  two  more 
crystallizations  of  the  same  product  from  acetone,  the  arsenic 
content  dropped  to  11.2*^  and  respectively. 

From  these  results  it  would  appear  that  p-carboxy  phenyl 
arsine  does  not  condenserwith  benzaldehyde  in  the  same  way 
that  phenyl  arsine  does.  Undoubtedly  a condensation  product 
of  some  kind  is  formed,  but  in  very  insignif iO;ant  yields. 

This  condensation  product  appeared  to  be  unstsabl%,  losing 


(1) 


method  of  Ewins 


A-fter  two  crystallizations  from  acetone 


(1)  Ewins,  J.  Chem.  Soc.,  109,  1356  (1916) 


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- 9 - 

arsenic  in  some  way,  when  boiled  with  acetone. 

The  results  of  the  attempt  to  prepare  snluble  members  of  the 
series,  C6H5As(CH0HR) 2,  using  p-carboxy  phenylarsine  as  the 
arsine  to  be  condensed  have  been  negative.  The  reactivity  of 
the  AsEg  group  in  these  condensations  may  be  effected  by  the 
presence  of  a carboxyl  group  in  the  ring.  Such  a difficulty 
mi^t  be  easily  overcome  by  using  an  arsine  of  phenyl  acetic 
acid,  such  as  p-H2AsCsH4CH2C00H.  The  effect  of  the  CHgCOOH  groiJp 
in  the  ring  should  approach  the  effect  of  a CHg  groijp,  in  any 
event  the  effect  should  be  markedly  different  than  that  produced 
by  a -COOH  directly  attached  to  the  ring.  In  case  the  presence 
of  a carboxyl  group  in  the  arsine  should  give  such  a conden- 
sation product  the  tendency  to  form  more  complex  condensations 
thru  the  carboxyl  group,  and  thereby  have  its  identity  de- 
stroyed, the  problem  mi^t  he  approached  from  another  angle, 
i.e.,  using  an  aldehyde  carrying  a salt  forming  group.  With 
such  an  aldehyde  as  p-hydroxy  benzaldehyde , phenyl  arsine 
might  readily  condense  to  give  a product  soluble  in  alkalies. 

SUMMARY  AND  CONCLUSIONS. 

1.  p-Garboxyphenyl  arsine  on  air  oxidation  is  not 
changed  simply  to  an  arsdno  compound  or  an  arsinic  acid,  but 
the  change  is  more  complex,  involing  the  carboxyl  group  in 
such  a way  that  its  identity  is  destroyed. 


J 


1 


« 10  - 

3.  Acetaldehy^de  does  not  condense  with  this  arsine,  but 
instead  seems  to  exert  an  oxidizing  effect  similar  to  exposure 
to  air. 

3.  Benzaldehyde  with  the  arsine  forms  small  amounts  of 
a condensation  product,  but  the  condensation  is  not  to  simplify 
to  the  formation  of  H00CC6H4As(CH0HCsH5) The  product  formed 
is  insoluble  in  alkalies  and  unstable  in  boiling  acetone. 


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